New strategies for mobilization of hematopoietic stem cells

Abstract

A significant number of tumor patients fail peripheral blood progenitor cell (PBPC) mobilization and thus cannot receive potentially curative high-dose chemotherapy with subsequently required PBPC transplantation. New insights into the physiology of mobilization have revealed the pivotal role of the CXCR4/stromal derived factor-1α receptor–ligand interaction for stem cell retention in the bone marrow. New CXCR4 antagonists such as AMD3100 are currently in clinical studies. They act synergistically with the established mobilizing agent granulocyte colony-stimulating factor (G-CSF); thus, patients can collect more PBPCs in fewer apheresis sessions, and others that previously failed can now successfully collect sufficient PBPCs for transplantation. Experimental and clinical data suggest that the quality of AMD3100-mobilized PBPC may even be superior to PBPCs mobilized following standard therapy. CXCR4 antagonists are the most exciting development in the field of PBPC mobilization for over a decade. Additionally, new analogs of G-CSF are being introduced with favorable pharmacologic features.